Nicotinamide Riboside in LVAD Recipients (PilotNR-LVAD)
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|ClinicalTrials.gov Identifier: NCT03727646|
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : November 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Heart Failure，Congestive Heart Failure New York Heart Association Class IV Mitochondrial Alteration||Dietary Supplement: Nicotinamide riboside||Early Phase 1|
This Pilot Study will examine the following Aims:
Aim 1: Enroll 5 participants scheduled for elective left ventricular assist device (LVAD) placement into an open-label study of nicotinamide riboside (NR).
a. Participants will have labs (including safety panels) drawn at baseline (Day 1), then receive escalating doses of NR to a maximum dose of 1000mg twice daily by Day 3. Participants will be continued on NR at 1000mg twice daily until LVAD implantation surgery.
On the morning of LVAD implantation Surgery (Day 5 or later), participants will have final labs drawn. Samples of fresh cardiac tissue removed from the left ventricular apex during LVAD implantation surgery will be collected in the operating room. The primary analyses will be performed on NR-treated participants who were on the maximum NR dose of 1000mg twice daily for at least 2 days prior to LVAD implantation surgery. The maximum duration of NR administration will be capped at 14 days. If the surgery doesn't happen by then, the participant will be withdrawn from the study.
Aim 2: Determine the effect of NR (as compared to historical controls) on levels of the oxidized and reduced forms of nicotine-adenine dinucleotide (NAD+ and NADH, respectively), mitochondrial function and its regulation through modifications of the epigenome in the failing myocardium.
- Measure NAD+ and NADH levels in the blood and myocardium of the participants.
- Assess mitochondrial morphology and function in cardiac tissue using, respectively, electron microscopy (EM) and isolated mitochondria.
- Determine protein acetylation in the mitochondrial and non-mitochondrial compartments and changes in nuclear gene regulation.
Aim 3: Test the hypothesis that NR improves mitochondrial function and reduces inflammatory response in heart failure (HF) patients receiving NR (as compared to historical controls).
- Measure mitochondrial function in peripheral blood mononucleated cells (PBMC).
- Determine the inflammatory response in PBMC.
- Compare effects on the circulating inflammasome vs. myocardial inflammation.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||This single-center, open-label study will compare blood and myocardial NAD+ levels and other mitochondrial endpoints in participants with end-stage heart failure treated with open-label nicotinamide riboside prior to LVAD implantation to similar endpoints from untreated patients previously undergoing LVAD implantation.|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||Study biostatistician will be blinded to group (NR vs. untreated controls)|
|Official Title:||Pilot Study of Preoperative Nicotinamide Riboside (Vitamin B3) Supplementation in Patients Undergoing Elective Left Ventricular Assist Device (LVAD) Implantation|
|Actual Study Start Date :||September 26, 2018|
|Estimated Primary Completion Date :||February 26, 2019|
|Estimated Study Completion Date :||July 26, 2019|
Experimental: Open-label nicotinamide riboside
Participants scheduled to receive an LVAD will be prescribed nicotinamide riboside (NR) according to the following administration schedule:
Dose Escalation Day 1: 250 mg (1 capsule) twice daily (total daily intake = 500 mg) Day 2: 500 mg (2 capsules) twice daily (total daily intake = 1000 mg) Day 3: 1000 mg (4 capsules) twice daily (total daily intake = 2000 mg)
Dose Maintenance Day 4: 1000 mg (4 capsules) twice daily Day 5-14 as applicable thru Day Before Surgery: 1000 mg (4 capsules) twice daily
Washout Day of LVAD Surgery and/or Day 15: None
Dietary Supplement: Nicotinamide riboside
nicotinamide riboside supplied as 250mg capsules
No Intervention: Baseline controls
Patients previously receiving LVADs, in whom blood and myocardial tissue assays for NAD+ levels and mitochondrial function were performed.
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: Up to 14 days ]Adverse Events
- Effect of NR on whole blood NAD+ levels [ Time Frame: Duration of NR treatment ]Change in whole blood NAD+ levels from Baseline to Day of Surgery in NR-treated participants
- Effect of NR on mitochondrial respiration (Seahorse assay) in isolated peripheral blood mononuclear cells (PBMCs) [ Time Frame: Up to 14 days ]Change in mitochondrial respiration from Baseline to Day of Surgery in NR-treated participants
- Between-group comparison of whole blood NAD+ levels [ Time Frame: Up to 14 days ]Comparison of whole blood NAD+ levels on the Day of LVAD Surgery in NR-treated vs. historical control patients
- Between-group comparison of mitochondrial respiration in PBMCs [ Time Frame: Up to 14 days ]Comparison of mitochondrial respiration in PBMCs on the Day of LVAD Surgery in NR-treated vs. historical control patients
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727646
|Contact: Laura McMartinfirstname.lastname@example.org|
|Contact: Fatemeh Ranjbaranemail@example.com|
|United States, Washington|
|University of Washington||Recruiting|
|Seattle, Washington, United States, 98195|
|Contact: Kevin D O'Brien, MD 206-529-7802 firstname.lastname@example.org|
|Contact: Rong Tian, MD 206 616-5672 email@example.com|
|Principal Investigator:||Kevin O'Brien, MD||University of Washington|